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Pangolins are the most trafficked wild animal in the world according to the World Wildlife Fund. The discovery of SARS-CoV-2-related coronaviruses in Malayan pangolins has piqued interest in the viromes of these wild, scaly-skinned mammals. We sequenced the viromes of 161 pangolins that were smuggled into China and assembled 28 vertebrate-associated viruses, 21 of which have not been previously reported in vertebrates. We named 16 members ofHunnivirus,PestivirusandCopiparvoviruspangolin-associated viruses. We report that thel-protein has been lost from all hunniviruses identified in pangolins. Sequences of four human-associated viruses were detected in pangolin viromes, including respiratory syncytial virus,Orthopneumovirus,RotavirusAandMammalian orthoreovirus. The genomic sequences of five mammal-associated and three tick-associated viruses were also present. Notably, a coronavirus related to HKU4-CoV, which was originally found in bats, was identified. The presence of these viruses in smuggled pangolins identifies these mammals as a potential source of emergent pathogenic viruses.

Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses. There is an ongoing debate as to whether established infections by one

Acute lung injury (ALI) is triggered by an acute inflammatory response. Lipopolysaccharide (LPS) is recognized as an important participant in the pathogenesis of sepsis, which may induce ALI. N-phenethyl-5-phenylpicolinamide (N5P) is a newly synthesized HIF-1α inhibitor. The purpose of the present study was to investigate the potential protective effects of N5P on LPS-induced ALI and the underlying mechanisms.In vivo experiment, the ALI rat model was induced by intratracheal injection of LPS, and various concentrations of N5P were injected intraperitoneally before LPS administration. In vitro experiment, RAW264.7 macrophages were administrated LPS and N5P to detect inflammatory cytokine changes. HIF-1α overexpression plasmid (HIF1α-OE) and granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycolysis agonist, were used to examine the relationship between the HIF-1α/glycolysis/ASIC1a pathway.Pretreatment with N5P inhibited not only the histopathological changes that occurred in the lungs but also lung dysfunction in LPS-induced ALI. N5P also decreased the levels of lactic acid in lung tissue and arterial blood, and inflammatory factors IL-1β and IL-6 levels in serum. LPS increased HIF-1α, glycolysis proteins GLUT1, HK2, ASIC1a, IL-1β, IL-6, and these changes were reversed by N5P in primary alveolar macrophages and RAW264.7 macrophages. Overexpression of HIF-1α significantly increased glycolysis genes and ASIC1a as well as inflammatory cytokines. Excessive glycolysis levels weaken the ability of N5P to inhibit inflammation.N5P may alleviate inflammation in ALI through the HIF-1α/glycolysis/ASIC1a signaling pathway. The present findings have provided pertinent information in the assessment of N5P as a potential, future therapeutic drug for ALI.

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

Blood-testis barrier (BTB) damage promotes spermatogenesis dysfunction, which is a critical cause of male infertility. Dyslipidemia has been correlated with male infertility, but the major hazardous lipid and the underlying mechanism remains unclear. In this study, we firstly discovered an elevation of palmitic acid (PA) and a decrease of inhibin B in patients with severe dyszoospermia, which leaded us to explore the effects of PA on Sertoli cells. We observed a damage of BTB by PA. PA penetration to endoplasmic reticulum (ER) and its damage to ER structures were exhibited by microimaging and dynamic observation, and consequent ER stress was proved to mediate PA-induced Sertoli cell barrier disruption. Remarkably, we demonstrated a critical role of aberrant protein palmitoylation in PA-induced Sertoli cell barrier dysfunction. An ER protein, Calnexin, was screened out and was demonstrated to participate in this process, and suppression of its palmitoylation showed an ameliorating effect. We also found that ω-3 poly-unsaturated fatty acids down-regulated Calnexin palmitoylation, and alleviated BTB dysfunction. Our results indicate that dysregulated palmitoylation induced by PA plays a pivotal role in BTB disruption and subsequent spermatogenesis dysfunction, suggesting that protein palmitoylation might be therapeutically targetable in male infertility.

Background The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. Methods In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. Results In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ2 test for trend, P P Conclusions Infectious diseases remain a substantial public health problem, and non-notifiable diseases should not be neglected. Multi-source-based big data are beneficial to better understand the profile and dynamics of infectious diseases.

Neutralization of SARS-CoV-2 Variants by Convalescent and Vaccinee Serum Analysis of serum samples from patients convalescing after SARS-CoV-2 infection and after vaccination with BBIBP-CorV or Cor...

The initial aim of environmental epidemiology is to estimate the causal effects of environmental exposures on health outcomes. However, due to lack of enough covariates in most environmental data sets, current methods without enough adjustments for confounders inevitably lead to residual confounding. We propose a negative-control exposure based on a time-series studies (NCE-TS) model to effectively eliminate unobserved confounders using an after-outcome exposure as a negative-control exposure. We show that the causal effect is identifiable and can be estimated by the NCE-TS for continuous and categorical outcomes. Simulation studies indicate unbiased estimation by the NCE-TS model. The potential of NCE-TS is illustrated by 2 challenging applications: We found that living in areas with higher levels of surrounding greenness over 6 months was associated with less risk of stroke-specific mortality, based on the Shandong Ecological Health Cohort during January 1, 2010, to December 31, 2018. In addition, we found that the widely established negative association between temperature and cancer risks was actually caused by numbers of unobserved confounders, according to the Global Open Database from 2003–2012. The proposed NCE-TS model is implemented in an R package (R Foundation for Statistical Computing, Vienna, Austria) called NCETS, freely available on GitHub.

In 2015, we evaluated 221 patients with undifferentiated fever and tick bite or animal exposure in Xinyang, China, for Rickettsia infection. Three with mild disease were infected with Candidatus R. xinyangensis, which clustered with R. fournieri and R. vini in phylogenetic analyses. Field investigations suggest Haemaphysalis longicornis ticks might be involved in transmission.

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors.Objective: The purpose of this research was to determine the serum miR-63...

Objectives Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. Methods A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013–2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. Results A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17–6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02–3.57) and MN (3.33, 1.26–9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08–2.63), underlying medical conditions (1.94, 95% CI 1.09–3.46) and lack of antiviral therapy (2.08, 95% CI 1.04–4.17) were predictors for higher T-cell responses. Conclusions Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.

Background Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). Methods This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18–59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Findings Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p

Respiratory syncytial virus (RSV) is an enveloped non-segmented negative sense RNA virus that belongs to Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales. The virus is the leading cause of severe respiratory disease in children under two years of age and is responsible for substantial disease burden in infants and elder people in both developed and developing countries

The large-scale production of a human diploid cell (HDC) vaccine (HDCV) for rabies is limited by several technical challenges. Kanghua Biological Products Co., Ltd., has successfully used microcarrier technology for the large-scale culture of HDCs in bioreactors to develop a lyophilized and purified HDCV. In this blinded, randomized, parallel-group study conducted between July and October 2014 in Mianzhu, Sichuan Province, China, we monitored the safety and immunogenicity of this vaccine in a healthy population vaccinated according to the Essen post-exposure immunization schedule. A hamster kidney cell vaccine was used as the control. Adverse reactions were monitored 0.5, 6, 24, 48, and 72 h post vaccination to assess safety. Neutralizing antibodies in venous blood were measured on day 7, 14, and 72 to evaluate the immunogenicity of the vaccine while follow-up monitoring continued for 1 month. No serious adverse reactions were observed in any volunteer. The incidence rates of systemic and local adverse reactions were, respectively, 10.6% and 2.9% in the test group and 20.0% and 13.6% in the control group. After the third injection, the positive conversion rates of antibodies in the test and control groups were 100% and 98.82%, respectively. In addition, the average antibody titers on day 7, 14, and 42, were respectively, 1.71, 2.72, and 1.29 times higher than those in the control group. These results indicate that HDCV had a better safety profile and higher immunogenicity than the hamster kidney cell rabies vaccine. Trial registration number: 20130602.

Background Hand foot and mouth disease (HFMD) is becoming one of the common human infectious diseases in China. Previous studies have described HFMD in tropical or coastal areas of Asia-Pacific countries. However, limited studies have thoroughly studied the epidemiology and potential risk factors for HFMD in inland areas with complex environmental conditions. Methodology/Principal findings Using the data from 2009 to 2018 on reported cases of Xinjiang Uighur Autonomous Region, we characterized the epidemic features of HFMD. Panel negative binomial model was used to identify climate, geographical and demographic determinants for HFMD incidence. A total of 70856 HFMD cases (average annual incidence: 305 per million persons) were reported in Xinjiang during the 10-year study period, of which 10393 (14.7%) were laboratory-confirmed and 98 (0.1%) were severe. HFMD peaked in summer every year during the study period, and incidence in 2012, 2015, 2016 and 2018 had minor peaks in autumn. After adjusting the school or holiday month, multiple factors were found to affect HFMD epidemiology: urban area being major land cover type (incidence risk ratio, IRR 2.08; 95% CI 1.50, 2.89), higher gross domestic product per capita (IRR 1.14; 95% CI 1.11, 1.16), rise in monthly average temperature (IRR 1.65; 95% CI 1.61, 1.69) and monthly accumulative precipitation (IRR 1.20; 95% CI 1.16, 1.24) predicted increase in the incidence of HFMD; farmland being major land cover type (IRR 0.72; 95% CI 0.64, 0.81), an increase of percentage of the minority (IRR 0.91; 95% CI 0.89, 0.93) and population density (IRR 0.98; 95% CI 0.98, 0.99) were related to a decrease in the incidence of HFMD. Conclusions/Significance In conclusion, the epidemic status of HFMD in Xinjiang is characterized by low morbidity and fatality. Multiple factors have significant influences on the occurrence and transmission of HFMD in Xinjiang., Author summary Hand foot and mouth disease (HFMD) is one of the common human infectious disease threating Asia-Pacific countries. To explore the epidemiology and environmental risk factors for HFMD in inland China, we utilized 10-year HFMD surveillance data in Xinjiang Uighur Autonomous Region and combined multiple spatial-temporal statistical analyses. We identified spatial-temporal clusters of HFMD incidence and found that multiple factors could affect HFMD incidence: urban area being major land cover type, higher gross domestic product per capita, rise in monthly average temperature and monthly accumulative precipitation predicted increase in the incidence of HFMD; farmland being major land cover type, an increase of percentage of the minority and population density were related to a decrease in the incidence of HFMD. Our findings facilitate the understanding of HFMD epidemiology and risk factors in different geographic regions, which are crucial for conducting prevention and control strategies of HFMD.

Dermacentor silvarum is an obligate blood sucking arthropod and transmits various pathogens to humans and domestic animals. Recently several new viruses were detected in D. silvarum as an emerging disease threat. In this study, we aimed to analyze its geographical distribution and associated pathogens. Data were collected from multiple sources, including a field survey, reference book, and literature review. We searched various electronic databases with the terms “Dermacentor silvarum” OR “D. silvarum” for studies published since 1963 and the positive rates for Dermacentor silvarum-associated pathogens were estimated by meta-analysis. D. silvarum was found only in four countries in Eurasia, ranging from 22° N to 57° N latitude. At least 20 human pathogens were associated with D. silvarum, including five species of spotted fever group rickettsiae, three species in the family of Anaplasmataceae, three genospecies in the complex Borrelia burgdorferi sensu lato, Francisella tularensis, Babesia venatorum, Coxiella buenetii, Borrelia miyamotoi, and five species of virus. Among them, Rickettsia raoultii was widely detected in D. silvarum, showing the highest pooled positive rate (25.15%; 95% CI 13.31–39.27). Our work presents the most comprehensive data and analysis (to our knowledge) for the geographical distribution of D. silvarum and associated pathogens, revealing an emerging threat to public health and stocking farming. Continued surveillance and further investigations should be enhanced.

Aims. Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), and macrophages play a key role in this process. The aim of this study was to discover the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition. Main Methods. We crossed lyz2-Cre mice with IKKα-floxed mice to generate mice with IKKα ablation in macrophages (Mac IKKα-/-). A mouse renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 minutes. Treated mice were evaluated for blood biochemistry, tissue histopathology, and fibrosis markers. Macrophages were isolated from the peritoneal cavity for coculturing with tubular epithelial cells (TECs) and flow cytometry analysis. Key Findings. We found that fibrosis and kidney function loss after IRI were significantly alleviated in Mac IKKα-/- mice compared with wild-type (WT) mice. The expression of fibrosis markers and the infiltration of M2 macrophages were decreased in the kidneys of Mac IKKα-/- mice after IRI. The in vitro experiment showed that the IRI TECs cocultured with IKKα-/- macrophages (KO MΦs) downregulated the fibrosis markers accompanied by a downregulation of Wnt/β-catenin signaling. Significance. These data support the hypothesis that IKKα is involved in mediating macrophage polarization and increasing the expression of fibrosis-promoting inflammatory factors in macrophages. Therefore, knockdown of IKKα in macrophages may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.

Western countries are experiencing surges in COVID-19 cases and deaths due to increasing public transportation during holiday seasons. This study aimed to explore whether mainland China will face an epidemic rebound during the Spring Festival holiday, when millions of Chinese people travel across the country, and investigate which nucleic acid testing (NAT) strategy is optimal to contain the epidemic. A microsimulation model was used to simulate SARS-CoV-2 transmission among railway travelers and evaluated the effects of various NAT strategies. An extended susceptible-exposed-infectious-recovered (SEIR) model was built to forecast local transmission during the Spring Festival period under different scenarios of testing strategies. The total number of infections, testing burden, and medical expenditure were calculated to devise an optimal strategy during the Spring Festival travel rush. Assuming the daily incidence of 20 per 10 million persons, our model simulated that there would be 97 active infections on the day of travel among 10 million railway passengers without NAT and symptom screening. Pre-travel testing could reduce the number of active infections. Compared with no NAT, testing passengers from risk tier 2–4 regions 3 days before travelling could significantly reduce the risk of transmission, and it is more economical and efficient than testing for all passengers.

OBF1 is a specific coactivator of the POU family transcription factors OCT1 and OCT2. OBF1 and OCT2 are B cell–specific and indispensable for germinal center (GC) formation, but their mechanism of action is unclear. Here, we show by chromatin immunoprecipitation-sequencing that OBF1 extensively colocalizes with OCT1 and OCT2. We found that these factors also often colocalize with transcription factors of the ETS family. Furthermore, we showed that OBF1, OCT2, and OCT1 bind widely to the promoters or enhancers of genes involved in GC formation in mouse and human GC B cells. Short hairpin RNA knockdown experiments demonstrated that OCT1, OCT2, and OBF1 regulate each other and are essential for proliferation of GC-derived lymphoma cell lines. OBF1 downregulation disrupts the GC transcriptional program: genes involved in GC maintenance, such as BCL6, are downregulated, whereas genes related to exit from the GC program, such as IRF4, are upregulated. Ectopic expression of BCL6 does not restore the proliferation of GC-derived lymphoma cells depleted of OBF1 unless IRF4 is also depleted, indicating that OBF1 controls an essential regulatory node in GC differentiation.

Background: The COVID-19 pandemic is challenging the public health response system worldwide, especially in poverty-stricken, war-torn, and least developed countries (LDCs). Methods: We characterized the epidemiological features and spread dynamics of COVID-19 in Niger, quantified the effective reproduction number (Rt ), evaluated the impact of public health control measures, and estimated the disease burden. Results: As of 4 July 2020, COVID-19 has affected 29 communes of Niger with 1093 confirmed cases, among whom 741 (67.8%) were males. Of them 89 cases died, resulting in a case fatality rate (CFR) of 8.1%. Both attack rates and CFRs were increased with age (P < 0.0001). Health care workers accounted for 12.8% cases. Among the reported cases, 39.3% were isolated and treated at home, and 42.3% were asymptomatic. 74.6% cases were clustered in Niamey, the capital of Niger. The Rt fluctuated in correlation to control measures at different outbreak stages. After the authorities initiated the national response and implemented the strictest control measures, Rt quickly dropped to below the epidemic threshold (

Vegetable crops have varied heavy metal(loid)s accumulation rates from soils to their edible tissues. However, crop selection has been seldom evaluated as a strategy for reducing the health risks of ingesting vegetables grown in soils contaminated by treated wastewater (TWW) irrigation. We cultivated twenty commonly grown vegetables using soils with an approximately 50-year history of TWW irrigation, and their ingestion risks were evaluated by the health risk index (HRI). Results showed that twenty vegetable species had varied abilities in accumulating heavy metal(loid)s from soils to their edible parts (e.g.,100 times of difference for Cd). We found higher potential health risks (HRI1) due to As, Cd, and Pb for adults ingesting few vegetable species and all the studied vegetables had negligible health risks (HRI1) for Cr, Cu, and Zn. These results suggest that remediation strategies should be targeted towards As, Cd, and Pb removal in agricultural soils in this region. Total HRI5 was obtained for ingesting spinach, Chinese lettuce, and Chinese chives, suggesting a high potential of severe health risks. Negligible risks (total HRI1) were found for tomato, kidney bean, potato, and cabbage. Our study highlights crop selection as a feasible strategy for ensuring food safety in TWW contaminated farmlands.

ObjectiveTo compare the epidemiological characteristics and transmission dynamics in relation to interventions against the COVID-19 and severe acute respiratory syndrome (SARS) outbreak in mainland China.DesignComparative study based on a unique data set of COVID-19 and SARS.SettingOutbreak in mainland China.ParticipantsThe final database included 82 858 confirmed cases of COVID-19 and 5327 cases of SARS.MethodsWe brought together all existing data sources and integrated them into a comprehensive data set. Individual information on age, sex, occupation, residence location, date of illness onset, date of diagnosis and clinical outcome was extracted. Control measures deployed in mainland China were collected. We compared the epidemiological and spatial characteristics of COVID-19 and SARS. We estimated the effective reproduction number to explore differences in transmission dynamics and intervention effects.ResultsCompared with SARS, COVID-19 affected more extensive areas (1668 vs 230 counties) within a shorter time (101 vs 193 days) and had higher attack rate (61.8 vs 4.0 per million persons). The COVID-19 outbreak had only one epidemic peak and one epicentre (Hubei Province), while the SARS outbreak resulted in two peaks and two epicentres (Guangdong Province and Beijing). SARS-CoV-2 was more likely to infect older people (median age of 52 years), while SARS-CoV tended to infect young adults (median age of 34 years). The case fatality rate (CFR) of either disease increased with age, but the CFR of COVID-19 was significantly lower than that of SARS (5.6% vs 6.4%). The trajectory of effective reproduction number dynamically changed in relation to interventions, which fell below 1 within 2 months for COVID-19 and within 5.5 months for SARS.ConclusionsChina has taken more prompt and effective responses to combat COVID-19 by learning lessons from SARS, providing us with some epidemiological clues to control the ongoing COVID-19 pandemic worldwide.

Healthcare workers (HCWs) worldwide are putting themselves at high risks of coronavirus disease 2019 (COVID-19) by treating a large number of patients while lacking protective equipment. We aim to provide a scientific basis for preventing and controlling the COVID-19 infection among HCWs. We used data on COVID-19 cases in the city of Wuhan to compare epidemiological characteristics between HCWs and non-HCWs and explored the risk factors for infection and deterioration among HCWs based on hospital settings. The attack rate (AR) of HCWs in the hospital can reach up to 11.9% in Wuhan. The time interval from symptom onset to diagnosis in HCWs and non-HCWs dropped rapidly over time. From mid-January, the median time interval of HCW cases was significantly shorter than in non-HCW cases. Cases of HCWs and non-HCWs both clustered in northwestern urban districts rather than in rural districts. HCWs working in county-level hospitals in high-risk areas were more vulnerable to COVID-19. HCW cases working in general, ophthalmology, and respiratory departments were prone to deteriorate compared with cases working in the infection department. The AR of COVID-19 in HCWs are higher than in non-HCWs. Multiple factors in hospital settings may play important roles in the transmission of COVID-19. Effective measures should be enhanced to prevent HCWs from COVID-19 infection.

A series of artemisinin-sulfonamide hybrids (1–16) have been designed and synthesized by using molecular hybridization approach and investigated for the inhibitory activity of four human (h) carbonic anhydrases (CAs, EC 4.2.1.1), hCA I, II, IX and XII. The results indicated most of the target compounds showed better CA IX and CA XII inhibitory activity than the starting segment sulfanilamide. Among all the compounds, compound 3 (IC50: 5 nM) showed the best CA IX inhibitory efficacy. The p-aminobenzenesulfonamide derivatives showed significant antiproliferative activities against MDA-MB-231 breast cancer cell line and HT-29 colon cancer cell line under hypoxic conditions where CA IX and CA XII are overexpressed and most of them showed no apparent cytotoxic effects toward MCF-10A normal mammary epithelial cell. Among these derivatives, compound 3 displayed the most potent antiproliferative activities (IC50: 0.65 μM) against HT-29 cell line under hypoxia and low cytotoxicity (IC50: 78.0 μM) toward normal cell line. Meanwhile, compound 3 was found to efficiently decrease the hypoxia-induced extracellular acidification in both cancer cells. Molecular docking studies of compounds 3, 4, 5 and 9 revealed the proper interactions between the hybrid molecules and the active site of CA IX. All the results proved the effectiveness of the hybridization approach to develop novel artemisinin-sulfonamide compounds targeting CA IX for cancer treatment.

The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with an increasing case number and extensive geographical expansion, raising concerns locally and globally; however, the description of its clinical features needs to be addressed by large studies. We aimed to determine all the clinical features of SFTS in a large population of patients in an endemic area.In this prospective observational study, data were collected on patients admitted to the People's Liberation Army Hospital in Xinyang, Henan Province, China, with laboratory-diagnosed SFTS. Demographic, clinical, laboratory, and treatment data were collected for each patient, and patients were followed up within 2 weeks after discharge or discontinuation of treatment. The association between each demographic, clinical, and laboratory variable with a fatal outcome was assessed. A clinical scoring model was designed for the early prediction of a fatal outcome, and the effect of treatment on outcome was analysed.Between April 1, 2011, and Oct 31, 2017, 2096 patients with laboratory-confirmed SFTS were admitted. Mean age at admission was 61·4 years (SD 12·2) and 1239 (59%) patients were female. The case fatality rate (CFR) was 16·2% (95% CI 14·6-17·8). A higher risk was associated with being male (unadjusted odds ratio [OR] 1·45, 95% CI 1·15-1·83; p=0·002), older age (for a 10-year increase, unadjusted OR 1·82, 95% CI 1·62-2·04; p0·0001), longer delay in admission (for every extra day taken before admission to hospital, unadjusted OR 1·18, 1·12-1·24; p0·0001), presence of diarrhoea (adjusted OR 1·44, 1·12-1·87; p=0·005) or dyspnoea (adjusted OR 8·35, 5·97-11·69; p0·0001), and development of haemorrhagic signs (adjusted OR 2·79, 95% CI 2·18-3·57; p0·0001) or neurological symptoms (adjusted OR 30·26, 21·39-42·81; p0·0001). Laboratory variables that were associated with death included abnormal concentrations of lactate dehydrogenase, aspartate aminotransferase, and blood urea nitrogen, and abnormal neutrophil percentage, which together with age and neurological symptoms were combined in the clinical scoring system. A total score of more than 8 was the optimal threshold to predict risk of death for patients who were evaluated within 6 days after symptom onset (area under the curve 0·879, 95% CI 0·855-0·902). For all participants, viraemia was a strong predictor of fatal outcome (all p0·0001). Ribavirin therapy was effective in reducing CFR from 6·25% (15 of 240 participants) to 1·16% (two of 173 participants), but only in patients with a viral load below 1×10The changing epidemiological features and high CFR of SFTS underscore the necessity of continued surveillance. Early prediction of fatal outcome can be attained by monitoring of clinical and laboratory data. Ribavirin should be applied early, with best results achieved before the viral load reaches 1 × 10National Natural Science Foundation of China.

Summary Background Transmission of infection through international travel is a growing health issue, and the frequency of imported infection is increasing in China. We aimed to quantify the total number of infections imported into mainland China by arriving travellers. Methods We actively surveyed arriving travellers at all 272 international entry–exit ports in mainland China. Suspected cases were detected through fever screening, medical inspection, self-declaration, and reporting by on-board staff. Participants completed a standardised questionnaire with questions about demographics, their travel itinerary (including detailed information about all countries or regions visited), and clinical manifestations. Nasopharyngeal swabs, sputum samples, faecal samples, vomitus, blood, and serum were collected as appropriate for diagnoses. Diagnosis was made by specific laboratory tests according to the national technical guidelines. Infections were classified as respiratory, gastrointestinal, vector-borne, blood-transmitted and sex-transmitted, or mucocutaneous. We divided arriving travellers into two groups: travellers coming from countries other than China, and travellers coming from Hong Kong, Macau, and Taiwan. We integrated surveillance data for 2014–16, calculated incidences of travel-related infections, and compared the frequency of infections among subgroups. Findings Between Jan 1, 2014, and Dec 31, 2016, 22 797 cases were identified among 805 993 392 arriving travellers—an overall incidence of 28·3 per million. 45 pathogens were detected in participants: 18 respiratory (19 662 cases), ten gastrointestinal (189 cases), seven vector-borne (831 cases), seven blood-transmitted and sex-transmitted (1531 cases), and three mucocutaneous (584 cases). Both the overall number and incidence of infection were more than five times higher in 2016 than in 2014. Case numbers and incidences also varied substantially by province, autonomous region, and municipality. Overall, 17 643 (77%) infections were detected by fever screening, but 753 (49%) blood-transmitted and sex-transmitted infections were identified through medical inspection. 14 305 (73%) cases of respiratory infection and 96 (51%) of gastrointestinal infections were in tourists. Tuberculosis, hepatitis A virus, vector-borne, and blood-transmitted and sex-transmitted infections were common among Chinese labourers who worked abroad. Dengue and malaria were most commonly diagnosed in travellers arriving from Africa. 12 126 (93%) of the 12 985 cases arriving from Hong Kong, Macau, or Taiwan were respiratory infections. Hand, foot, and mouth disease accounted for 2·90% of infections in travellers from Hong Kong, Macau, or Taiwan and 0·31% of infections in international travellers. Interpretation This report is the first to characterise the profile of travel-related infections among arriving travellers in mainland China. Our findings should increase public awareness of the potential risk of imported infections, and help health-care providers to make evidence-based health recommendations to travellers. Funding The Natural Science Foundation of China.

We conducted a 3-year longitudinal serologic survey on an open cohort of poultry workers, swine workers, and general population controls to assess avian influenza A virus (AIV) seroprevalence and seroincidence and virologic diversity at live poultry markets (LPMs) in Wuxi City, Jiangsu Province, China. Of 964 poultry workers, 9 (0.93%) were seropositive for subtype H7N9 virus, 18 (1.87%) for H9N2, and 18 (1.87%) for H5N1. Of 468 poultry workers followed longitudinally, 2 (0.43%), 13 (2.78%), and 7 (1.5%) seroconverted, respectively; incidence was 1.27, 8.28, and 4.46/1,000 person-years for H7N9, H9N2, and H5N1 viruses, respectively. Longitudinal surveillance of AIVs at 9 LPMs revealed high co-circulation of H9, H7, and H5 subtypes. We detected AIVs in 726 (23.3%) of 3,121 samples and identified a high diversity (10 subtypes) of new genetic constellations and reassortant viruses. These data suggest that stronger surveillance for AIVs within LPMs and high-risk populations is imperative.

Chang-chun Cao,1,* Da-wei Chen,2,* Jing Li,2 Meng-qing Ma,2 Yu-bao Chen,3 Yi-zhi Cao,4 Xi Hua,2 Wei Shao,1 Xin Wan2 1Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 2Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 4The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11days versus 8days; P = 0.020), longer hospitalization (14days versus 12days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03–2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes. Keywords: acute exacerbation of COPD, community-acquired acute kidney injury, hospital-acquired acute kidney injury, short-term outcomes

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection typically causes acute fever, thrombocytopenia and leucopenia, presenting with a high case fatality rate. The pathogenesis of SFTSV infection, however, is not well described. It was hypothesized that endothelial dysfunction might play part in the disease process. In current study, we retrospectively analyzed the clinical manifestations among a large group of confirmed SFTS cases and found evidence of plasma leakage and vascular endothelial injury. Then we established a SFTSV infection cell model and determined the infectivity and stimulation of SFTSV on vascular endothelial cells in vitro. The hyperpermeability of endothelial cells directly induced by SFTSV was confirmed by electrical resistance and dextran diffusion assay. The virus induced alterations of cell junctions and cytoskeleton was also revealed. It's suggested that vascular endothelial cell injury and barrier function damage were induced after SFTSV infection, which is a vital but neglected pathogenesis of SFTS.

Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016–February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for

Background Human babesiosis is an emerging health problem in China. Methods Babesia were identified in ticks, sheep, and humans in northeastern China using polymerase chain reaction (PCR) followed by genetic sequencing. We enrolled residents who experienced a viral-like illness after recent tick bite or were healthy residents. We defined a case using the definition for babesiosis developed by the US Centers for Disease Control and Prevention. Results A Babesia crassa-like agent was identified in Ixodes persulcatus and Haemaphysalis concinna ticks using PCR followed by sequencing. The agent was characterized through phylogenetic analyses of the 18S rRNA gene, the β-tubulin gene, and the internal transcribed spacer region. We tested sheep as a possible reservoir and found that 1.1% were infected with the B. crassa-like agent. We screened 1125 human participants following tick bites using B. crassa-specific PCR and identified 31 confirmed and 27 suspected cases. All the patients were previously healthy except for 1 with an ovarian tumor. Headache (74%), nausea or vomiting (52%), and fever (48%) were the most common clinical manifestations of confirmed cases. Six of 10 cases remained PCR positive for B. crassa-like infection 9 months after initial diagnosis. Asymptomatic infections were detected in 7.5% of 160 local residents. Conclusions We identified B. crassa-like infection in people in northeastern China that caused mild to moderate symptoms. The possibility of more severe disease in immunocompromised patients and of transmission through the blood supply due to asymptomatic infections justifies further investigation of this reported infection.

We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.

In this paper, a new class of novel sulfonamides incorporating aminosaccharide tails were designed and synthesized based on the sugar-tail approach. Then, all the novel compounds were evaluated for their inhibitory activities against three carbonic anhydrase (CA, EC 4.2.1.1) isoenzymes (hCA I, hCA II and hCA IX). Interestingly, effective inhibition of these three CA isoforms were observed, especially the glaucoma associated isoform hCA II. It is worth noting that these glycoconjugated sulfonamide derivatives also showed better CA inhibitory effects compared to the initial segment carzenide. Among them, compound 8d was the most effective inhibitor with IC50 of 60 nM against hCA II. Subsequent physicochemical properties studies showed that all compounds have good water solubility and neutral pH values in solutions. And these important physicochemical properties make target compounds acquire obvious advantages in the preparation of topical and nonirritating antiglaucoma drugs. Moreover, the target compounds showed lower corneal cytotoxicity than acetazolamide (AAZ) and good metabolic stability in vitro. In addition, molecular docking studies confirmed the interactions between aminosaccharide fragment and hydrophilic subpocket of hCA II active site were crucial for the enhanced CA inhibitory activity. Taken together, these results suggested 8d would be a promising lead compound for the development of topical antiglaucoma CAIs.

With the increasing incidence of antifungal resistance, new antifungal agents having novel scaffolds hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. In this study, we reported the design, synthesis, and pharmacological evaluation of novel 1,2,3-selenadiazole analogues by scaffold hopping strategy. Preliminary results of antifungal activity demonstrated that the new class of compounds showed broad-spectrum fungistatic and fungicidal activity. Most importantly, these newly synthesized compounds can eliminate these azole-resistant fungi and inhibit the formation of C. albicans biofilm. In particular, compound S07 showed promising antifungal activity against five azole-resistant strains with MIC values ranging from 4 to 32 μg/mL. Then, further target identification and mechanistic studies indicated that representative compound S07 exert its inhibitory activity by inhibiting fungal lanosterol 14α-demethylase enzyme (CYP51). Interestingly, representative compounds showed low cytotoxicity on mammalian cell lines. In addition, the molecular docking studies elucidated the binding modes of these compounds toward CYP51. Altogether, these results suggest that compound S07 with novel skeleton is a promising CYP51 inhibitor for treatment of fungal infections.

ObjectiveTo evaluate epidemiological characteristics and transmission dynamics of COVID-19 outbreak resurged in Beijing and to assess the effects of three non-pharmaceutical interventions.DesignDescriptive and modelling study based on surveillance data of COVID-19 in Beijing.SettingOutbreak in Beijing.ParticipantsThe database included 335 confirmed cases of COVID-19.MethodsTo conduct spatiotemporal analyses of the outbreak, we collected individual records on laboratory-confirmed cases of COVID-19 from 11 June 2020 to 5 July 2020 in Beijing, and visitor flow and products transportation data of Xinfadi Wholesale Market. We also built a modified susceptible-exposed-infected-removed model to investigate the effect of interventions deployed in Beijing.ResultsWe found that the staff working in the market (52.2%) and the people around 10 km to this epicentre (72.5%) were most affected, and the population mobility entering-exiting Xinfadi Wholesale Market significantly contributed to the spread of COVID-19 (p=0.021), but goods flow of the market had little impact on the virus spread (p=0.184). The prompt identification of Xinfadi Wholesale Market as the infection source could have avoided a total of 25 708 (95% CI 13 657 to 40 625) cases if unnoticed transmission lasted for a month. Based on the model, we found that active screening on targeted population by nucleic acid testing alone had the most significant effect.ConclusionsThe non-pharmaceutical interventions deployed in Beijing, including localised lockdown, close-contact tracing and community-based testing, were proved to be effective enough to contain the outbreak. Beijing has achieved an optimal balance between epidemic containment and economic protection.

Background Rickettsia raoultii is frequently detected in multiple tick species, whereas human infection remains scarcely studied. Methods A surveillance study was performed at 3 sentinel hospitals in China, to recruit participants with suspected tick exposure. Rickettsia raoultii infection was identified through polymerase chain reaction, followed by sequencing, and confirmed serologically. Isolation by cell culture was performed and the isolates were genome sequenced. Results Twenty-six subjects were determined to have R. raoultii infection, including 7 with asymptomatic infection, 15 with mild to moderate illness, and 4 with severe illness. Common nonspecific manifestations in the 19 patients with mild to moderate or severe illness included fever (100%), malaise (95%), myalgia (58%), lymphadenopathy (53%), and nausea (42%). Only 5% of them had rash, and 16% had eschar. Scalp eschar and neck lymphadenopathy after a tick bite syndrome was only seen in 2 patients. Of the 4 patients with severe complications, 3 developed pulmonary edema, and 1 developed clouding of consciousness and lethargy. Frequent abnormalities of laboratory testing included leukopenia, thrombocytopenia, lymphopenia, neutropenia, hypoproteinemia, and elevated levels of total bilirubin, hepatic aminotransferases, lactate dehydrogenase, and creatine kinase. All the 19 patients recovered without sequelae after receiving doxycycline treatment. Two R. raoultii strains were isolated, and a significantly less degraded genome was observed than other more virulent Rickettsia strains, indicating a low pathogenicity of the current strain. Conclusions Human infection with R. raoultii has a wide clinical spectrum that ranged from subclinical infection to severe complications. Physicians need to be aware of the high potential and clinical complexity of R. raoultii infection, to ensure appropriate testing and treatment in endemic regions.

Wei-Wei Xu,1,* Da-yu Liu,2,* Ying-chun Cao,1 Xiang-yun Wang1 1Department of Ear-Nose-Throat, Dongying People’s Hospital, Dongying, 2ENT & HN Surgery Department, Qilu Hospital, Shandong University, Jinan, Shandong, China *These authors contributed equally to this work Abstract: In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2–siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2–siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells. Keywords: laryngeal cancer, docetaxel, ABCG2–siRNA, anti-tumor efficacy, liposomal chemotherapy carriers, GE11 peptide-targeted liposomes

Tick-borne encephalitis (TBE) has become an increasing public health threat in recent years, ranging from Europe, through far-eastern Russia to Japan and northern China. However, the neglect of its expansion and scarce analyses of the dynamics have made the overall disease burden and the risk distribution of the disease being unclear in mainland China. In this study, we described epidemiological characteristics of 2117 reported human TBE cases from 2006 to 2013 in mainland China. About 99% of the cases were reported in forest areas of northeastern China, and 93% of reported infections occurred during May-July. Cases were primarily male (67%), mostly in 30-59 years among all age-gender groups. Farmers (31.6%), domestic workers (20.1%) and forest workers (17.9%) accounted for the majority of the patients, and the proportions of patients from farmers and domestic workers were increasing in recent years. The epidemiological features of TBE differed slightly across the affected regions. The distribution and features of the disease in three main endemic areas of mainland China were also summarized. Using the Boosted Regression Trees (BRT) model, we found that the presence of TBE was significantly associated with a composite meteorological index, altitude, the coverage of broad-leaved forest, the coverage of mixed broadleaf-conifer forest, and the distribution of Ixodes persulcatus (I. persulcatus) ticks. The model-predicted probability of presence of human TBE cases in mainland China was mapped at the county level. The spatial distribution of human TBE in China was largely driven by the distributions of forests and I. persulcatus ticks, altitude, and climate. Enhanced surveillance and intervention for human TBE in the high-risk regions, particularly on the forest areas in north-eastern China, is necessary to prevent human infections.

Background This study examined the feasibility of transabdominal intestinal ultrasonography in evaluating acute gastrointestinal injury (AGI). Methods A total of 116 patients were included. Intestinal ultrasonography was conducted daily within 1 week after admission to the intensive care unit. Ultrasonography indicators including intestinal diameter, changes in the intestinal folds, thickness of the intestinal wall, stratification of the intestinal wall, and intestinal peristalsis (movement of the intestinal contents) were observed to determine the acute gastrointestinal injury ultrasonography (AGIUS) score. The gastrointestinal and urinary tract sonography ultrasound (GUTS) protocol score was also calculated. During the first week of the study, the gastrointestinal failure (GIF) score was determined daily. The correlations between transabdominal intestinal scores (AGIUS and GUTS) and the GIF score were analyzed to clarify the feasibility of evaluating AGI through observation of the intestine. The utility of intestinal ultrasonography indicators in predicting feeding intolerance was investigated to improve the ability of clinicians to manage AGI. Results A total of 751 ultrasonic examinations were performed with 511 images (68%) considered to be of “good quality.” AGIUS and GUTS scores differed significantly between AGI patients (GIF score 0–2) and non-AGI patients (GIF score 3–4) (p r = 0.54, p r = 0.66, p 10/min) have increased risk for feeding intolerance (16/83 vs. 25/33, p Conclusions The transabdominal intestinal ultrasonography represents an effective means for assessing gastrointestinal injury in critically ill patients. Intestinal ultrasonography indicators, especially the degree of intestinal peristalsis, may be used to predict feeding intolerance. Trial registration ClinicalTrial.gov, NCT03589248. Registered 04 July 2018—retrospectively registered.

Background A tick-borne segmented RNA virus called Jingmen tick virus (JMTV) was recently identified, variants of which were detected in a non-human primate host and fatal patients with Crimean-Congo haemorrhagic fever. We investigated its infectivity and pathogenicity for humans. Methods We obtained skin-biopsy, blood and serum samples from patients with tick bites, and used high-throughput sequencing, in situ hybridisation, and serologic testing to diagnose and ascertain the cases of JMTV infection. Findings A JMTV strain was isolated from the tick Amblyomma javanense into an embryo-derived tick cell line. We obtained sustained passage of JMTV, and revealed that it was able to accumulate in salivary glands of experimentally infected ticks. Four JMTV-infected patients were identified by high-throughput sequencing of skin biopsies and blood samples. The virus replication in skin tissue was visualised by in situ hybridisation. The four patients all had an itchy or painful eschar at the site of tick bite, with or without lymphadenopathy. Immunohistochemical examination revealed remarkable local inflammation manifested as infiltration by neutrophils. Eight patients were identified by serological testing and showed more severe clinical manifestations. Two Ixodes persulcatus ticks detached from patients were positive for JMTV. All JMTV strains identified in this study formed a well-supported sub-lineage, distinct from those previously reported in China. Interpretation The public significance of JMTV should be highly concerning due to its potential pathogenicity for humans and efficient transmission by potential ticks. Fund China Natural Science Foundation, State Key Research Development Programme, and United Kingdom Biotechnology and Biological Sciences Research Council.

To assess the efficacy and safety of endovenous laser treatment (EVLT) and high ligation (HL) for limb varicosity using meta-analysis. Multiple databases including PubMed, Springer, Excerpta Medica Database, Ovid Technologies, and China Journal Full-text database were searched for relevant studies in English or Chinese, and full-text articles were used to compare EVLT and HL for limb varicosity. Review Manager 5.0 was used to estimate the effects of the results among eligible articles. Forest plots, sensitivity analysis, and bias analysis of the included articles were also conducted. Initial screening yielded 1031 studies, 11 randomised controlled trials involving 1145 limb varicosity patients met the inclusion criteria in this study. The results of the heterogeneity test suggested that intraoperative blood loss mean difference (MD) = -6.31[-9.03, -3.60], P < 0.00001), operative time (MD) = -39.76[-42.27, -37.24], P < 0.00001), rate of complications (odds ratio [OR] = 0.37[0.22, 0.61], P < 0.0001), and recurrence (OR = 0.28[0.16, 0.49], P < 0.0001) were significantly different. Although both EVLT and HL have their own merits and demerits, EVLT is a more effective and safe method to treat limb varicosity.

Utilizing the Social Cognitive Career Theory (SCCT) as the theoretical framework, this study proposed a moderated mediation model investigating the complex functioning mechanisms of how self-efficacy beliefs and leader support can be related to research motivation among Chinese university teachers. A group of 310 Chinese teachers working in different universities completed an online survey. Results from structural equation modeling (SEM) analysis revealed distinct influencing paths from the predictor variables (i.e., self-efficacy and leader support) to the outcome variables (i.e., intrinsic and extrinsic research motivation). Specifically, self-efficacy beliefs predicted both mastery and performance goal orientations; mastery goal orientation, in turn, positively affected intrinsic and extrinsic research motivation. In contrast, leader support was non-significant for the both types of goal orientations, but exerted strong direct influences on the both types of research motivation. Bootstrapping methods in SEM showed that it was primarily the mastery goal orientation that mediated the relationships between self-efficacy beliefs and research motivation. Furthermore, the results from the SEM and simple slope analysis revealed that leader support moderated the association between self-efficacy and extrinsic research motivation.

Background For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis. Case presentation This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures. Conclusions This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years.

Background Hypercatabolism is associated with increased infectious rates and mortality in critically ill patients. Enteral nutrition (EN) is usually used to counteract hypercatabolism. However, the impact of different routes of EN on hypercatabolism remains unknown. Here, we compared the impact of gastric feeding (GF) and jejunal feeding (JF) on gastrointestinal hormones and hypercatabolism, which is associated with hypothalamic adenosine 5'-monophosphate-activated protein kinase (AMPK)-autophagy-proopiomelanocortin (POMC). Methods Sixty adult male Sprague-Dawley rats were divided into 5 groups: Sham and lipopolysaccharide (LPS) groups fed a standard chow diet, a pair-fed group that was a subset of saline-treated rats pair-fed with the LPS group, and LPS + JF and LPS + GF groups (received EN via jejunal and gastric tube, respectively, for 3 days [100 kcal/kg/d]). Hypercatabolism was measured by insulin resistance, muscle protein synthesis, and atrophy. Serum gastrointestinal hormones, hypothalamic ghrelin, growth hormone secretagogue receptor-1α (GHS-R1α), and AMPK-autophagy-POMC markers were also detected. Results GF increased serum total, acylated, desacylated, and hypothalamic ghrelin and decreased glucagon-like peptide-1 (GLP-1). But no effect on pancreatic polypeptide (PYY) and hypothalamic GHS-R1α was observed. JF showed no effect on hypothalamic ghrelin, GHS-R1α, and serum total, acylated, and desacylated ghrelin and even further aggravated GLP-1 and PYY. GF could effectively augment hypothalamic AMPK-autophagy-POMC and hypercatabolism. However, JF showed no effect on hypothalamic AMPK-autophagy-POMC and hypercatabolism. Conclusions GF could activate hypothalamic AMPK-autophagy and suppress POMC expression via gastrointestinal hormones to ameliorate hypercatabolism compared with JF, which suggested that GF may be the preferred route of EN in endotoxemic rats.

During 2013-2015 in central China, co-infection with spotted fever group rickettsiae was identified in 77 of 823 patients infected with severe fever with thrombocytopenia syndrome virus. Co-infection resulted in delayed recovery and increased risk for death, prompting clinical practices in the region to consider co-infection in patients with severe fever with thrombocytopenia syndrome.

// Xiao-Ai Zhang 1 , Chen-Tao Guo 2 , Qing-Bin Lu 3 , Jian-Gong Hu 1 , Ning Cui 4 , Zhen-Dong Yang 4 , Wei Peng 5 , Rong Liu 1 , Chun-Yan Hu 1 , Shu-Li Qin 4 , Xian-Jun Wang 6 , Shu-Jun Ding 6 , Dou-Dou Huang 1, 2 , Wei Liu 1, 2 , Wu-Chun Cao 1 1 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, P. R. China 2 Graduate School of Anhui Medical University, Hefei, 230032, P. R. China 3 School of Public Health, Peking University, Beijing, 100191, P. R. China 4 The 154 Hospital, People’s Liberation Army, Xinyang, 464000, P. R. China 5 The Shangcheng People’s Hospital, Xinyang, 464000, P. R. China 6 Shandong Provincial Center for Disease Control and Prevention, Jinan, 250001, P. R. China Correspondence to: Wu-Chun Cao, email: caowc@bmi.ac.cn Wei Liu, email: lwbime@163.com Keywords: severe fever with thrombocytopenia syndrome, polymorphism, susceptibility, PDGF-B, cytokines Received: December 06, 2015 Accepted: April 11, 2016 Published: April 27, 2016 ABSTRACT Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV). We hypothesize that host genetic variations may contribute to susceptibility to SFTS. Results: Compared with the rs1800818 AA genotype, AG + GG genotypes were significantly associated with increased susceptibility to SFTS (odds ratio, 1.66, 95% confidence interval = 1.28-2.16; P < 0.001). By using the ELISA assay, we observed that PDGF-BB concentration was significantly reduced in acute phase of patients than in the controls ( P < 0.001) and recovered patients at 6 month ( P = 0.007) and 12 month ( P = 0.003). A persistently reduced PDGF-BB was also revealed from the SFTSV-infected C57BL/6J mice ( P < 0.001). The rs1800818 G allele was associated with decreased serum PDGF-BB levels in SFTS patients at their early infection ( P = 0.015). In accordance, the relative mRNA levels of the at-risk G allele of 1800818 were lower than those of the A allele in heterozygous cell from acute phase of SFTS patients. PDGF-B rs1800818 conferred no susceptibility to severe or fatal outcome in SFTS patients. Materials and Methods: An initially small-scale case-control association study guided the selection of platelet derived growth factor-B ( PDGF-B ) rs1800818 in 1020 SFTS patients and 1353 controls. Functional analyses were conducted to verify the biological significance of rs1800818 polymorphism. Conclusions: Our findings suggest that the PDGF-B rs1800818 polymorphism might play a role in mediating the susceptibility to SFTS.

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.